Trending of systolic murmur intensity for monitoring cardiac disease with implantable device

ABSTRACT

Described is an implantable device configured to monitor for changes in the intensity and/or duration of a systolic murmur such as mitral regurgitation by means of an acoustic sensor. Such changes may be taken to indicate a change in a patient&#39;s heart failure status. Upon detection of a worsening in the patient&#39;s heart failure statue, the device may be programmed to alert clinical personnel over a patient management network and/or make appropriate adjustments to pacing therapy.

FIELD OF THE INVENTION

This invention pertains to cardiac devices such as pacemakers and othertypes of devices for monitoring and treating cardiac dysfunction.

BACKGROUND

Heart failure (HF) refers to a condition in which the heart fails topump enough blood to satisfy the needs of the body. It is usually due tosome damage to the heart itself, such as from a myocardial infarction orheart attack. When heart failure occurs acutely, autonomic circulatoryreflexes are activated that both increase the contractility of the heartand constrict the vasculature as the body tries to defend against thedrop in blood pressure. Venous constriction, along with the reduction inthe heart's ability to pump blood out of the venous and pulmonarysystems (so-called backward failure), causes an increase in thediastolic filling pressure of the ventricles. This increase in preload(i.e., the degree to which the ventricles are stretched by the volume ofblood in the ventricles at the end of diastole) causes an increase instroke volume during systole, a phenomena known as the Frank-Starlingprinciple. If the heart failure is not too severe, this compensation isenough to sustain the patient at a reduced activity level. When moderateheart failure persists, other compensatory mechanisms come into playthat characterize the chronic stage of heart failure. The most importantof these is the depressing effect of a low cardiac output on renalfunction. The increased fluid retention by the kidneys then results inan increased blood volume and further increased venous return to theheart. A state of compensated heart failure results when the factorsthat cause increased diastolic filling pressure are able to maintaincardiac output at a normal level even while the pumping ability of theheart is compromised.

Compensated heart failure, however, is a precarious state. If cardiacfunction worsens or increased cardiac output is required due toincreased activity or illness, the compensation may not be able tomaintain cardiac output at a level sufficient to maintain normal renalfunction. Fluid then continues to be retained, causing the progressiveperipheral and pulmonary edema that characterizes overt congestive heartfailure. Diastolic filling pressure becomes further elevated whichcauses the heart to become so dilated and edematous that its pumpingfunction deteriorates even more. This condition, in which the heartfailure continues to worsen, is decompensated heart failure. It can bedetected clinically, principally from the resulting pulmonary congestionand dyspnea, and all clinicians know that it can lead to rapid deathunless appropriate therapy is instituted.

SUMMARY

Described herein is a method by which an implantable cardiac device maymonitor a patient's heart failure status. The method involves measuringthe intensity of a systolic murmur with an acoustic sensor incorporatedinto the device. Upon detecting an increase in the intensity of themurmur, the device may be configured to transmit an alarm message over apatient management network. In another embodiment, the device isconfigured to deliver pacing therapy which may be altered and/orinitiated upon detection of an increase in murmur intensity.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the physical placement of an implantable cardiacdevice.

FIG. 2 illustrates an exemplary implantable device for monitoringsystolic murmurs as well as delivering pacing therapy.

FIG. 3 is a block diagram of a system for measuring systolic murmurintensity.

FIGS. 4 and 5 illustrate exemplary algorithms which may be implementedin an implantable device.

DETAILED DESCRIPTION

The tricuspid and mitral valves, also referred to as theatrioventricular or AV valves, separate the atrium and ventricle on theright and left sides of heart, respectively. The function of theatrioventricular valves is to allow flow of blood between the atrium andventricle during ventricular diastole and atrial systole but prevent thebackflow of blood during ventricular systole. The mitral valve iscomposed of a fibrous ring called the mitral annulus located between theleft atrium and the left ventricle, the anterior and posterior leaflets,the chordae tendineae, and the papillary muscles. The leaflets extendfrom the mitral annulus and are tethered by the chordae tendineae to thepapillary muscles which are attached to the left ventricle. The functionof the papillary muscles is to contract during ventricular systole andlimit the travel of the valve leaflets back toward the left atrium. Ifthe valve leaflets are allowed to bulge backward into the atrium duringventricular systole, called prolapse, leakage of blood through the valvecan result. The structure and operation of the tricuspid valve issimilar.

Mitral regurgitation (MR), also referred to as mitral insufficiency ormitral incompetence, is characterized by an abnormal reversal of bloodflow from the left ventricle to the left atrium during ventricularsystole. This occurs when the leaflets of the mitral valve fail to closeproperly as the left ventricle contracts, thus allowing retrograde flowof blood back into the left atrium. Tricuspid regurgitation (TR) occursin a similar manner. MR and TR can be due to a variety of structuralcauses such as ruptured chordae tendineae, leaflet perforation, orpapillary muscle dysfunction. Functional MR and TR may also occur inheart failure patients due to annular dilatation or myocardialdysfunction, both of which may prevent the valve leaflets from coaptingproperly.

In certain patients, the severity of MR is known to increase withworsening heart failure. In the events leading up to HF decompensation,the presence of volume and/or pressure overload and ventricular dilationresult in advancement of valvular insufficiency due to, for example,extra tension on the papillary muscles and chordae tendineae as well asdistortion of the mitral annulus. A worsening of left ventricularsystolic function also implies an elevation of mean left atrial pressurewhich increases the severity of MR.

Described herein is system which may be incorporated into an implantablecardiac device with a capability of sensing murmurs is used to monitorchanges in the intensity and duration of murmurs in a chronic ambulatorymanner. In conjunction with an in-home or portable patient monitoringsystem by which the implantable device may transmit messages over anetwork, changes in the severity of systolic murmurs (such as MR) may beused to alert physicians and caregivers of worsening cardiac diseaseand, in particular, decompensated heart failure. Monitoring for changesin the severity of MR is a viable means for monitoring the severity ofheart failure that is independent of other measures such as right-sidedpressures, pulmonary fluid status, and respiration rate.

The system for sensing murmurs includes an acoustic sensor (e.g., amicrophone or other type of pressure sensor) with sufficient bandwidth(e.g., 1 Khz) to detect at least moderate levels of systolic mitralvalve insufficiency. In different embodiments, the acoustic sensor is apressure sensor integrated with a pacing lead, a dedicated pressuresensor either leadless or with a lead, or a microphone mounted on thesurface of the implantable device housing. Electrograms provided by thesensing channels of the implantable device may be used to identify thesystolic phase of the cardiac cycle, and signal processing techniquesmay be used to detect and measure attributes of the murmur. Theseattributes can be measured repeatedly throughout the day and used toform a trend. The murmur baseline may be established during a periodwhere the disease status of the patient is known to be stable.Significant changes from the baseline can be used to generate an alarmmessage, or can be combined with information from other sensors to makea blended sensor decision.

In an exemplary embodiment, envelope detection of broadband acousticenergy in a band between 200 Hz and up to 1 Khz is used to measuremurmur intensity. Harmonic heart sound components (e.g., S1 and S2) maybe filtered out or ignored. Measurement of the intensity, duration andtiming of the murmur relative to the systolic phase of the cardiac cycleare made and may be repeated multiple times. The multiple measurementscan be statistically combined to generate a composite daily measurement.The algorithm for detection of a significant change in the murmur mayalso take into account the variability of the daily measurements byusing tests of statistical significance to declare those measurementsthat are different from an established baseline, thus offering a meansof adjustment of sensitivity and specificity.

Described below is an exemplary implantable device into which may beincorporated a system for monitoring systolic murmur intensity. Thedevice may or may not include other functionality such as cardiacpacing. As is explained, however, in a device with pacing functionality,changes in systolic murmur intensity may also be used to triggercompensatory alterations in pacing therapy.

1. Exemplary Device Description

As shown in FIG. 1, an implantable cardiac device 1 for deliveringpacing therapy (a.k.a., a pacemaker) is typically placed subcutaneouslyor submuscularly in a patient's chest with leads 200 threadedintravenously into the heart to connect the device to electrodes 300used for sensing and pacing of the atria and/or ventricles. Electrodesmay also be positioned on the epicardium by various means. Aprogrammable electronic controller causes the pacing pulses to be outputin response to lapsed time intervals and sensed electrical activity(i.e., intrinsic heart beats not as a result of a pacing pulse). Thedevice senses intrinsic cardiac electrical activity through a sensingchannel which incorporates internal electrodes disposed near the chamberto be sensed. A depolarization wave associated with an intrinsiccontraction of the atria or ventricles that is detected by the device isreferred to as an atrial sense or ventricular sense, respectively. Inorder to cause such a contraction in the absence of an intrinsic beat, apacing pulse with energy above a certain threshold is delivered to thechamber through a pacing channel which incorporates internal electrodesdisposed near the chamber to be paced.

A block diagram of an implantable multi-site pacemaker having multiplesensing and pacing channels is shown in FIG. 2. The controller of thepacemaker is made up of a microprocessor 10 communicating with a memory12 via a bidirectional data bus, where the memory 12 typically comprisesa ROM (read-only memory) for program storage and a RAM (random-accessmemory) for data storage. The controller is capable of operating thepacemaker in a number of programmed modes where a programmed modedefines how pacing pulses are output in response to sensed events andexpiration of time intervals. A telemetry transceiver 80 is provided forcommunicating with an external device 300 such as an externalprogrammer. An external programmer is a computerized device with anassociated display and input means that can interrogate the pacemakerand receive stored data as well as directly adjust the operatingparameters of the pacemaker. The telemetry transceiver 80 enables thecontroller to communicate with an external device 300 via a wirelesstelemetry link. The external device 300 may be an external programmerwhich can be used to program the implantable device as well as receivedata from it or may be a remote monitoring unit. The external device 300may also be interfaced to a patient management network 91 enabling theimplantable device to transmit data and alarm messages to clinicalpersonnel over the network as well as be programmed remotely. Thenetwork connection between the external device 300 and the patientmanagement network 91 may be implemented by, for example, an internetconnection, over a phone line, or via a cellular wireless link.

The embodiment shown in FIG. 2 has multiple sensing/pacing channels,where a pacing channel is made up of a pulse generator connected to anelectrode while a sensing channel is made up of the sense amplifierconnected to an electrode. A MOS switching network 70 controlled by themicroprocessor is used to switch the electrodes from the input of asense amplifier to the output of a pulse generator. The switchingnetwork 70 also allows the sensing and pacing channels to be configuredby the controller with different combinations of the availableelectrodes. The channels may be configured as either atrial orventricular channels allowing the device to deliver conventionalventricular single-site pacing, biventricular pacing, or multi-sitepacing of a single chamber, where the ventricular pacing is deliveredwith or without atrial tracking. In an example configuration, threerepresentative sensing/pacing channels are shown. A right atrialsensing/pacing channel includes ring electrode 43 a and tip electrode 43b of bipolar lead 43 c, sense amplifier 41, pulse generator 42, and achannel interface 40. A right ventricular sensing/pacing channelincludes ring electrode 23 a and tip electrode 23 b of bipolar lead 23c, sense amplifier 21, pulse generator 22, and a channel interface 20,and a left ventricular sensing/pacing channel includes ring electrode 33a and tip electrode 33 b of bipolar lead 33 c, sense amplifier 31, pulsegenerator 32, and a channel interface 30. The channel interfacescommunicate bi-directionally with a port of microprocessor 10 andinclude analog-to-digital converters for digitizing sensing signalinputs from the sensing amplifiers, registers that can be written to foradjusting the gain and threshold values of the sensing amplifiers, andregisters for controlling the output of pacing pulses and/or changingthe pacing pulse amplitude. In this embodiment, the device is equippedwith bipolar leads that include two electrodes which are used foroutputting a pacing pulse and/or sensing intrinsic activity. Otherembodiments may employ unipolar leads with single electrodes for sensingand pacing. The switching network 70 may configure a channel forunipolar sensing or pacing by referencing an electrode of a unipolar orbipolar lead with the device housing or can 60.

The controller controls the overall operation of the device inaccordance with programmed instructions stored in memory and implementsthe systolic murmur monitoring function as described herein. Thecontroller interprets electrogram signals from the sensing channels,implements timers for specified intervals, and controls the delivery ofpaces in accordance with a pacing mode. The sensing circuitry of thepacemaker generates atrial and ventricular electrogram signals from thevoltages sensed by the electrodes of a particular channel. Anelectrogram indicates the time course and amplitude of cardiacdepolarization and repolarization that occurs during either an intrinsicor paced beat. When an electrogram signal in an atrial or ventricularsensing channel exceeds a specified threshold, the controller detects anatrial or ventricular sense, respectively, which pacing algorithms mayemploy to trigger or inhibit pacing. An impedance sensor 95 is alsointerfaced to the controller for measuring transthoracic impedance. Thetransthoracic impedance measurement may be used to derive eitherrespiratory minute ventilation for rate-adaptive pacing modes or, asdescribed below, cardiac stroke volume for monitoring heart failurestatus.

2. Exemplary System for Monitoring Systolic Murmurs

Also shown in FIG. 2 is a pressure sensor 100 which is interfaced to thecontroller and allows the device to monitor for changes in the intensityor duration in a systolic murmur such as MR. FIG. 3 illustrates aparticular embodiment of a system for sensing a systolic murmur whichmay be incorporated into the implantable device. The pressure sensor 100is adapted for disposition so as to sense the acoustic vibrationsproduced by a systolic murmur (e.g., disposed in the pulmonary artery)and is connected to the implantable device by an intravascular lead or alead-less type of link (e.g., an ultrasonic or RF link). Afterdigitization by analog-to-digital converter 101, the signal from thepressure sensor 100 is filtered by a bandpass filter 102 which may beimplemented in code executed by the device controller. In this example,the filter's passband is from 100 Hz to 500 Hz which represents a bandwhich is fairly specific for the frequency components of a murmur due toMR. Other passbands could be used to tailor the filtering for apatient's specific murmur. The filtered pressure signal is next passedto a signal energy detector 103, also implemented as code executed bythe controller, which measures the signal energy in the filteredpressure signal which may be taken to represent the intensity of themurmur. An R-wave detector (i.e., detection of a ventricular sense bythe device) 104 enables the energy detector to measure the intensity ofthe murmur during the systolic phase of the cardiac cycle. Thecontroller may also measure the duration of the murmur during thesystolic phase. Changes in either the intensity or duration of themurmur from baseline values may be used as an indicator of a change inthe patient's heart failure status.

FIG. 4 illustrates an exemplary algorithm which may be executed by thecontroller to monitor for changes in a systolic murmur and report suchchanges to clinical personnel so that intervention may be initiated ifappropriate. At step A1, the patient's baseline murmur intensity isrecorded. At step A2, the patient's current murmur intensity ismeasured, where the current murmur intensity may be an average ofintensity measurements taken over some period of time in order toaverage out insignificant variations. At step A3, the current murmurintensity is compared with the baseline value to determine if theintensity has increased by a specified threshold amount. If not, stepsA2 and A3 are repeated on a continuous or periodic basis. If the murmurintensity has increased by the specified threshold amount, an alarm flagis set and an alarm message is transmitted to over the patientmanagement network via telemetry at step A4. If the device is configuredto deliver pacing therapy, such therapy may also be adjusted at step A5in response to the change in murmur intensity. As explained below, suchpacing therapy adjustments may involve cardiac resynchronization pacing.

The device may also record the murmur intensity measurements in order todetermine if a trend exists. For example, if the device determines thatthe patient's murmur intensity is increasing at a rate above a specifiedthreshold value, an alarm flag could be set and an alarm message sentover the patient management network even if the murmur intensity is notabove the baseline value by the specified threshold amount. Automaticadjustments to pacing therapy could also be made in response to adetected trend. FIG. 5 illustrates an exemplary algorithm. At step B1,multiple intensity measurements are taken during the day (or otherdefined time period) and stored. At step B2, the stored intensitymeasurements are statistically combined (e.g., averaged) to yield acomposite intensity measurement for the day. At step B3, the positive ornegative differences between consecutive daily composite intensitymeasurements over some period of time (e.g., a week or a month) arecomputed and summed to give the net increase or decrease in intensityover the period of time, thus representing the trend in the murmur'sintensity. This trend is then compared with a specified threshold valueat step B4. If the trend is positive and greater than the threshold, analarm flag is set and an alarm message is transmitted to over thepatient management network via telemetry at step B5.

The algorithms discussed above with reference to FIGS. 4 and 5 monitorfor changes in murmur intensity as an indicator of heart failure status.The same steps could also be performed with respect to murmur durationas changes in the duration of a systolic murmur can also be due tochanges in heart failure status. Also, the device may use other sensingmodalities to monitor for changes in other parameters besides murmurintensity and duration which may be indicative of either worsening MR orheart failure. Changes in these additional parameters may then be usedby the device to more specifically detect if a change in heart failurestatus has taken place. For example, if the pressure sensor is disposedin the pulmonary artery, the device may measure the pulmonary pressureas an estimate of mean left atrial pressure which increases as theseverity of MR increases. The device could then be programmed to set analarm flag if the current murmur intensity exceeds the baseline murmurintensity by a specified threshold amount only if the left atrialpressure during also exceeds another specified threshold amount. Anotherway in which the extent of mitral regurgitation and/or heart failurestatus may be monitored is via a transthoracic impedance measurementreflective of cardiac volume during the cardiac cycle. As mitralregurgitation produces volume overloading of both the left atrium andventricle, an increase in, for example, end-diastolic left ventricularvolume above a specified threshold may be used as an indication that thepatient's MR or heart failure has worsened.

As noted above, changes in a patient's heart failure status as detectedby systolic murmur monitoring may also be used to adjust pacing therapydelivered by the device. Ventricular resynchronization therapy is mostcommonly applied in the treatment of patients with heart failure due toleft ventricular dysfunction which is either caused by or contributed toby left ventricular conduction abnormalities. In such patients, the leftventricle or parts of the left ventricle contract later than normalduring systole which thereby impairs pumping efficiency. In order toresynchronize ventricular contractions in such patients, pacing therapyis applied such that the left ventricle or a portion of the leftventricle is pre-excited relative to when it would become depolarized inan intrinsic contraction. Optimal pre-excitation for treating aconduction deficit in a given patient may be obtained with biventricularpacing or with left ventricular-only pacing. If the device is configuredto deliver resynchronization therapy, such therapy could be initiatedupon detection of a worsening in the patient's heart failure status.Alternatively, pacing parameters could be adjusted in order to increasethe amount of pre-excitation delivered by the therapy. For example, theAV delay used in atrial tracking pacing modes could be decreased, or thebiventricular offset used to pre-excite one ventricle (usually the leftventricle) could be increased.

In an exemplary embodiment, an implantable cardiac device comprises apressure sensor adapted for disposition so as to sense the acousticvibrations produced by a systolic murmur; a bandpass filter forfiltering the pressure signal; a signal energy detector for measuring aparameter related to the signal energy of the filtered pressure signalto represent the murmur intensity; a controller programmed to record abaseline murmur intensity; and, wherein the controller is furtherprogrammed to measure a current murmur intensity as an average ofintensity measurements taken over some period of time, compare thecurrent murmur intensity to the baseline murmur intensity, and set analarm flag if the current murmur intensity exceeds the baseline murmurintensity by a specified threshold amount. The device may furthercomprise a pressure sensor adapted for disposition in the pulmonaryartery which is configured to measure the pulmonary pressure and whereinthe controller is programmed to set an alarm flag if the current murmurintensity exceeds the baseline murmur intensity by a specified thresholdamount only if the pulmonary pressure also exceeds another specifiedthreshold amount.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Other such alternatives, variations, and modifications are intended tofall within the scope of the following appended claims.

1. An implantable cardiac device, comprising: a pressure sensor adaptedfor disposition in the pulmonary artery of a patient in order to measurepulmonary artery pressure; means for obtaining an intensity measurementof a systolic murmur; and, a controller programmed to measure a currentmurmur intensity as an average of intensity measurements taken over someperiod of time, record a baseline murmur intensity, compare the currentmurmur intensity to the baseline murmur intensity, and set an alarm flagif the current murmur intensity exceeds the baseline murmur intensity bya first specified threshold amount and if the pulmonary artery pressureexceeds a second specified threshold amount.
 2. The device of claim 1wherein the controller is programmed to measure a current duration ofthe murmur during the systolic phase, compare the current murmurduration to a baseline murmur duration, and set an alarm flag if thecurrent murmur duration exceeds the baseline murmur duration by aspecified threshold amount.
 3. The device of claim 1 further comprisingan R-wave detector for enabling the signal energy detector to measurethe intensity of the murmur during the systolic phase of the cardiaccycle.
 4. The device of claim 1 further comprising a telemetrytransceiver and wherein the controller is programmed to transmit analarm message over a patient management network via telemetry if thecurrent murmur intensity exceeds the baseline murmur intensity by aspecified threshold amount.
 5. The device of claim 1 wherein thecontroller is further programmed to store the current murmur intensitymeasurements take over a specified period time and compute a trend inthe murmur's intensity.
 6. The device of claim 5 wherein the trend iscomputed by computing differences between consecutive current murmurintensity measurements over the specified period of time and summing thedifferences.
 7. The device of claim 1 further comprising circuitry forpacing the heart in a programmed mode and wherein the controller isprogrammed to adjust the programmed mode if the current murmur intensityexceeds the baseline murmur intensity by a specified threshold amount.8. The device of claim 7 wherein the device is configured to pace theheart in an atrial triggered mode and wherein the controller isprogrammed to adjust a programmed AV delay if the current murmurintensity exceeds the baseline murmur intensity by a specified thresholdamount.
 9. The device of claim 7 wherein the device is configured topace the heart in a biventricular pacing mode and wherein the controlleris programmed to adjust a biventricular offset if the current murmurintensity exceeds the baseline murmur intensity by a specified thresholdamount.
 10. A method, comprising: measuring the intensity of a systolicmurmur and recording a baseline murmur intensity; measuring thepulmonary artery pressure; and, measuring a current murmur intensity asan average of intensity measurements taken over some period of time,comparing the current murmur intensity to the baseline murmur intensity,and setting an alarm flag if the current murmur intensity exceeds thebaseline murmur intensity by a first specified threshold amount and themeasured pulmonary artery pressure exceeds a second specified thresholdamount.
 11. The method of claim 10 further comprising measuring acurrent duration of the murmur during the systolic phase, comparing thecurrent murmur duration to a baseline murmur duration, and setting analarm flag if the current murmur duration exceeds the baseline murmurduration by a specified threshold amount.
 12. The method of claim 10further comprising detecting R-wave in order to measure the intensity ofthe murmur during the systolic phase of the cardiac cycle.
 13. Themethod of claim 10 further comprising transmitting an alarm message overa patient management network via telemetry if the current murmurintensity exceeds the baseline murmur intensity by a specified thresholdamount.
 14. The method of claim 10 further comprising storing thecurrent murmur intensity measurements take over a specified period timeand computing a trend in the murmur's intensity.
 15. The method of claim14 wherein the trend is computed by computing differences betweenconsecutive current murmur intensity measurements over the specifiedperiod of time and summing the differences.
 16. The method of claim 10further comprising pacing the heart in a programmed mode and adjustingthe programmed mode if the current murmur intensity exceeds the baselinemurmur intensity by a specified threshold amount.
 17. The method ofclaim 16 further comprising pacing the heart in an atrial triggered modeand adjusting a programmed AV delay if the current murmur intensityexceeds the baseline murmur intensity by a specified threshold amount.18. The method of claim 16 further comprising pacing the heart in abiventricular pacing mode and adjusting a biventricular offset if thecurrent murmur intensity exceeds the baseline murmur intensity by aspecified threshold amount.